Chrysin attenuates cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity.

Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, Romania.

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Department of Hematology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, Romania.

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Institute of Life Sciences, Vasile Goldis Western University of Arad, and University of Medicine and Pharmacy Victor Babes, Timisoara, Romania.

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Institute of Life Sciences, Vasile Goldis Western University of Arad, Romania.

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Department of Public Health and Management, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, Romania.

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Department of Intensive Care Unit, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, Romania.

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Department of Cardiac surgery, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, Romania.

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Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, and Institute of Life Sciences, Vasile Goldis Western University of Arad, Romania. anca.hermenean@gmail.com.

Abstract

Chrysin (CHR) is a natural flavonoid and is present in high concentration in honey, propolis and many plant extracts. The aim of the present study was to evaluate the effects of CHR to reduce cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity. Morphology of the cardiomyocytes was determined by optic and transmission electron microscopy and biochemistry methods. The expression of Bcl-2, Bax and Caspase-3 were assessed by immunofluorecence. Tunel assay was used to assess apoptosis in cardiomyocytes. In addition, the distribution of desmin protein was evaluated using immunohistochemistry. Our results show that MTX treatment significantly increased serum levels of creatine kinase isoenzyme (CK-MB), indicator of cardiac injury and withdrawn under CHR protection. Expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following MTX treatment. 50 mg/kg of daily CHR intake reduced Bax and caspase-3 immunopositivity and restored Bcl-2 levels to a value comparable to the control. TUNEL (+) cardiomyocyte nuclei of MTX group showed typical signs of apoptosis which almost completely disappeared in response to 50 mg/kg CHR treatment. In parallel, an irregular distribution and a weak expression of desmin is associated with MTX induced cardiotoxic effects which was also restored by CHR treatment. In conclusion chrysin inhibits MTX-triggered cardiomyocyte apoptosis via multiple pathways, including decrease of the Bax/Bcl-2 ratio and caspase-3 expression along with preservation of the desmin disarray.